| Objective: Membraneous nephropathy(MN)is one of the most common pathological types in adult nephrotic syndrome.Most patients eventually develop end-stage renal failure.The main clinical feature of the disease is a large amount of proteinuria and a gradual decline in renal function.They can be divided into idiopathic membranous nephropathy(IMN)and secondary membranous nephropathy(SMN)according to the cause.At present,the diagnosis of IMN still depends on renal biopsy.Therefore,we need to find a safe,fast and effective non-invasive index for the diagnosis of IMN and determine its role in the development of IMN.Previous studies have found that compared with healthy controls,the expression of miR-451 a,miR-17,miR-106 a,and miR-19 b in plasma of patients with focal segmental glomerulosclerosis(FSGS)is significantly down-regulated.This suggests that the above four miRNAs play important roles in the pathogenesis of FSGS.FSGS and IMN are both typical podocyte diseases.We speculate that the above four miRNAs may also be down-regulated in IMN patients.Therefore,the purpose of this study is to verify the expression of miR-451 a,miR-17,miR-106 a and miR-19 b in the serum of IMN patients,and to confirm the possible mechanism of action of these miRNAs,in order to find new biomarkers for IMN And lay the foundation for studying the role of miRNAs in the development of IMN.Methods: In this study,55 cases of serum samples of IMN patients confirmed by renal biopsy were selected as the case group,and 58 healthy physical examination patients were used as the control group.Real-time PCR was used to detect miR-451 a,miR-17,miR-106 a and miR-19 b.Then analyze the expression differences of the above four miRNAs between the case group and the control group,use ROC to analyze the diagnostic efficacy of various indicators.Targetscan was used to predict the target genes,and the difference of target protein expression between the case group and the control group was verified by ELISA experiments.Results: Compared with the healthy control group,the serum levels of miR-106a(p=0.0077),miR-19b(p<0.0001),and miR-17(p=0.0006)in the IMN group were significantly reduced,the miR-451a(p=0.84)was not significantly different between the two groups.In the ROC analysis,the areas under the ROC curves of miR-106 a,miR-19 b,and miR-17 were 0.66(95% confidence interval=0.5585 to 0.7618),0.81(95% confidence interval=0.7257 to 0.8899),and 0.69(95% confidence interval=0.5930 to 0.7881).Compared with the healthy control group,the concentrations of phosphatase and tensin homolog(PTEN)protein in the serum of IMN patients were significantly increased,and the difference was statistically significant(p<0.0001),and there was a negative correlation between PTEN protein concentration and miR-19 b.24 hour urine protein quantification,Scr,Cysc and Urea were positively correlated with PTEN protein concentration,while Alb was negatively correlated with it.In the correlation analysis between miR-19 b expression and clinical data,miR-19 b was negatively correlated with Urea and Cysc,positively correlated with Alb and e GFR,and the rest were not correlated.Conclusion: The serum levels of miR-17,miR-106 a and miR-19 b in IMN patients were significantly down-regulated.This result indicates that they play a key role in the occurrence and development of IMN,and may become diagnostic indicators of IMN disease.miR-19 b may regulate podocyte apoptosis by inhibiting the expression of PTEN. |
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